Circulation, Vol 90, 2385-2389, Copyright © 1994 by American Heart Association
JS Ginsberg, MT Nurmohamed, M Gent, B MacKinnon, J Sicurella, P Brill-Edwards, MN Levine, AA Panju, P Powers and P Stevens
BACKGROUND--The study objective was to determine whether Hirulog, a direct
thrombin inhibitor, has potential efficacy and safety in the prevention of
deep vein thrombosis (DVT) in orthopedic patients. A phase 2 open-label,
dose-escalating design was used to study 222 unselected patients undergoing
major hip or knee surgery in tertiary- care, university-affiliated
hospitals. METHODS AND RESULTS-- Subcutaneous Hirulog was initiated
postoperatively. Patients were evaluated for bleeding and symptomatic
pulmonary embolism, and mandatory bilateral venography was performed before
discharge. Dose escalations were made on the basis of observed rates of
bleeding and venous thrombosis. There were five dosage regimens used: 0.3
mg/kg every 12 hours, 0.6 mg/kg every 12 hours, 1.0 mg/kg every 12 hours
for 3 days followed by 0.6 mg/kg every 12 hours for up to 11 days, 1.0
mg/kg every 12 hours, and 1.0 mg/kg every 8 hours. One hundred seventy-
seven patients who had technically adequate bilateral venography or
objectively documented pulmonary embolism were included in the primary
analysis of efficacy. The highest dosage regimen (1.0 mg/kg every 8 hours)
provided the lowest rates of total DVT (17%) and proximal DVT (2%), both of
which were significantly lower (P = .010 and P = .023, respectively) than
the pooled rates of total (43%) and proximal (20%) DVT seen with the first
four regimens. Bleeding rates were low (< 5%) with all regimens.
CONCLUSIONS--This study demonstrates that 1.0 mg/kg Hirulog every 8 hours
started postoperatively is potentially efficacious and safe for the
prevention of DVT after major hip or knee surgery.
ARTICLES
Use of Hirulog in the prevention of venous thrombosis after major hip or knee surgery
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
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